Neurodevelopmental disorder and late‐onset degenerative parkinsonism in a patient with a WDR45 defect

2021 ◽  
Author(s):  
Filippo Manti ◽  
Celeste Panteghini ◽  
Barbara Garavaglia ◽  
Vincenzo Leuzzi
Keyword(s):  
Late Onset ◽  
Neurodevelopmental Disorder ◽  
Degenerative Parkinsonism

Response to Steroids in IQSEC2-Related Encephalopathy Presenting with Rett-Like Phenotype and Infantile Spasms

2020 ◽  
Author(s):  
Divya Nagabushana ◽  
Aparajita Chatterjee ◽  
Raghavendra Kenchaiah ◽  
Ajay Asranna ◽  
Gautham Arunachal ◽  
...  
Keyword(s):  
Late Onset ◽  
Neurodevelopmental Disorder ◽  
Epileptic Encephalopathy ◽  
Infantile Spasms ◽  
The Past ◽  
Resource Limited ◽  
The Central Nervous System ◽  
Motor Milestone ◽  
Behavior And Cognition ◽  
Atypical Rett Syndrome

Abstract Introduction IQSEC2-related encephalopathy is an X-linked childhood neurodevelopmental disorder with intellectual disability, epilepsy, and autism. This disorder is caused by a mutation in the IQSEC2 gene, the product of which plays an important role in the development of the central nervous system. Case Report We describe the symptomatology, clinical course, and management of a 17-month-old male child with a novel IQSEC2 mutation. He presented with an atypical Rett syndrome phenotype with developmental delay, autistic features, midline stereotypies, microcephaly, hypotonia and epilepsy with multiple seizure types including late-onset infantile spasms. Spasms were followed by worsening of behavior and cognition, and regression of acquired milestones. Treatment with steroids led to control of spasms and improved attention, behavior and recovery of lost motor milestone. In the past 10 months following steroid therapy, child lags in development, remains autistic with no further seizure recurrence. Conclusion IQSEC2-related encephalopathy may present with atypical Rett phenotype and childhood spasms. In resource-limited settings, steroids may be considered for spasm remission in IQSEC2-related epileptic encephalopathy.

scholarly journals Is late-onset Attention Deficit Hyperactivity Disorder (ADHD) a valid diagnosis in adults?

2018 ◽  
Vol 97 (1) ◽  
pp. 71-80
Author(s):  
Mauro Xavier Neto ◽  
Sofia Amaral Medeiros ◽  
Arthur de Campos Soares ◽  
Renério Fráguas Junior
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Age Of Onset ◽  
Late Onset ◽  
Neurodevelopmental Disorder ◽  
Adult Life ◽  
Clinical Aspects ◽  
Hyperactivity Disorder ◽  
Current State ◽  
Pubmed Search

INTRODUCTION: The current Attention Deficit Hyperactivity Disorder (ADHD) paradigm understands it as a childhood-onset neurodevelopmental disorder that can persist into adult life. However, it has been raised the possibility of a late-onset ADHD syndrome. OBJECTIVE: Evaluate the current state of knowledge regarding late-onset (i.e. age-of-onset > 12 years) ADHD. MATERIAL AND METHODS: Systematic literature review using PubMed (MEDLINE) and SCOPUS databases. RESULTS: We found six studies reporting data offering some support for the existence of late-onset ADHD: five from the PubMed search and one from the non-overlapping articles in the SCOPUS search. DISCUSSION: Despite the small number of studies, the differences in methodology among them and the presence of limitations in all of them, data regarding clinical aspects offer some support for the content validity of late-onset ADHD diagnosis in adults. CONCLUSIONS: Although many controversies still exist and studies supporting its construct validity are needed, late-onset ADHD may be a valid diagnosis in adults. Thus, clinicians should consider diagnosing and treating late-onset ADHD in adults, instead of just neglecting this possibility because of the age-of-onset criterion.

scholarly journals KCND3-Related Neurological Disorders: From Old to Emerging Clinical Phenotypes

2020 ◽  
Vol 21 (16) ◽  
pp. 5802
Author(s):  
Luca Pollini ◽  
Serena Galosi ◽  
Manuela Tolve ◽  
Caterina Caputi ◽  
Carla Carducci ◽  
...  
Keyword(s):  
Movement Disorders ◽  
Early Onset ◽  
Neurological Disorder ◽  
De Novo ◽  
Age Of Onset ◽  
Late Onset ◽  
Wide Spectrum ◽  
Neurodevelopmental Disorder ◽  
Clinical Phenotypes ◽  
K Current

KCND3 encodes the voltage-gated potassium ion channel subfamily D member 3, a six trans-membrane protein (Kv4.3), involved in the transient outward K+ current. KCND3 defect causes both cardiological and neurological syndromes. From a neurological perspective, Kv4.3 defect has been associated to SCA type 19/22, a complex neurological disorder encompassing a wide spectrum of clinical features beside ataxia. To better define the phenotypic spectrum and course of KCND3-related neurological disorder, we review the clinical presentation and evolution in 68 reported cases. We delineated two main clinical phenotypes according to the age of onset. Neurodevelopmental disorder with epilepsy and/or movement disorders with ataxia later in the disease course characterized the early onset forms, while a prominent ataxic syndrome with possible cognitive decline, movement disorders, and peripheral neuropathy were observed in the late onset forms. Furthermore, we described a 37-year-old patient with a de novo KCND3 variant [c.901T>C (p.Ser301Pro)], previously reported in dbSNP as rs79821338, and a clinical phenotype paradigmatic of the early onset forms with neurodevelopmental disorder, epilepsy, parkinsonism-dystonia, and ataxia in adulthood, further expanding the clinical spectrum of this condition.

scholarly journals Mouse Models Characterize GNAO1 Encephalopathy as a Neurodevelopmental Disorder Leading to Motor Anomalies: from a Severe G203R to a Milder C215Y Mutation

2021 ◽  
Author(s):  
Denis Silachev ◽  
Alexey Koval ◽  
Mikhail Savitsky ◽  
Guru Padmasola ◽  
Charles Quairiaux ◽  
...  
Keyword(s):  
Mouse Models ◽  
De Novo ◽  
Late Onset ◽  
Wide Spectrum ◽  
Neurodevelopmental Disorder ◽  
Point Mutations ◽  
Clinical Manifestations ◽  
Epileptic Seizures ◽  
Motor Dysfunction ◽  
Neuronal Precursor Cells

Abstract GNAO1 encephalopathy characterized by a wide spectrum of neurological deficiencies in pediatric patients originates from de novo heterozygous mutations in the gene encoding Gαo, the major neuronal G protein. Efficient treatments and even the proper understanding of the underlying etiology are currently lacking for this dominant disease. Adequate animal models of GNAO1 encephalopathy are urgently needed. Here we describe establishment and characterization of mouse models of the disease based on two point mutations in GNAO1 with different clinical manifestations. One of them is G203R leading to the early-onset epileptic seizures, motor dysfunction, developmental delay and intellectual disability. The other is C215Y producing much milder clinical outcomes, mostly – late-onset motor hyperactivity. The resultant mouse models show distinct phenotypes: severe neonatal lethality in GNAO1[G203R]/+ mice vs. normal vitality in GNAO1[C215Y]/+. The latter model further revealed strong hyperactivity and hyperlocomotion in a panel of behavioral assays, without signs of epilepsy, recapitulating the patients’ manifestations. Importantly, despite these differences the two models similarly revealed prenatal brain developmental anomalies, such as enlarged lateral ventricles and decreased numbers of neuronal precursor cells in the cortex. Thus, our work unveils GNAO1 encephalopathy as to a large extent neurodevelopmental malady. We expect that this understanding and the tools we established will be instrumental for future therapeutic developments.

The neurodevelopmental nature of attention-deficit hyperactivity disorder in adults

2020 ◽  
Vol 218 (1) ◽  
pp. 43-50
Author(s):  
Vitor Breda ◽  
Luis Augusto Rohde ◽  
Ana Maria Baptista Menezes ◽  
Luciana Anselmi ◽  
Arthur Caye ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Latent Class ◽  
Mixed Model ◽  
Late Onset ◽  
Neurodevelopmental Disorder ◽  
Age At Onset ◽  
Factors Associated ◽  
Hyperactivity Disorder ◽  
Persistent Symptoms

BackgroundPopulation studies have suggested that most adults with attention-deficit hyperactivity disorder (ADHD) did not have the disorder in childhood, challenging the neurodevelopmental conceptualisation of ADHD. Arbitrary definitions of age at onset and lack of defined trajectories were accounted for the findings.AimsThe objective of this study was to assess the proportion of individuals presenting with either a neurodevelopmental trajectory or late-onset disorder, and to assess risk factors associated with them.MethodData of 4676 individuals from the 1993 Pelotas birth cohort at 11, 15, 18 and 22 years of age were used. Polythetic and latent class mixed model analyses were performed to define ADHD trajectories from childhood to adulthood, and characterise the neurodevelopmental or late-onset courses. Regression models were applied to assess factors associated with different trajectories.ResultsClassical polythetic analyses showed that 67% of those with ADHD at 22 years of age had a neurodevelopmental course of the disorder. Latent class mixed model analysis indicated that 78% of adults with ADHD had a trajectory of persistent symptoms, more common in males. The remaining adults with ADHD had an ascending symptom trajectory that occurred after puberty, with late-onset ADHD associated with female gender and higher IQ.ConclusionsBoth polythetic and latent trajectories analyses provided empirical evidence supporting that the large majority of adults with ADHD had a neurodevelopmental disorder.

scholarly journals De Novo Variants in EEF2 Cause a Neurodevelopmental Disorder with Benign External Hydrocephalus

2020 ◽  
Author(s):  
Maria J Nabais Sá ◽  
Alexandra N Olson ◽  
Grace Yoon ◽  
Graeme A M Nimmo ◽  
Christopher M Gomez ◽  
...  
Keyword(s):  
De Novo ◽  
Late Onset ◽  
Neurodevelopmental Disorder ◽  
Elongation Factor ◽  
Missense Variant ◽  
Bioinformatic Analysis ◽  
Cellular Growth ◽  
Mild Phenotype ◽  
Motor Delay ◽  
External Hydrocephalus

Abstract Eukaryotic translation elongation factor 2 (eEF2) is a key regulatory factor in gene expression that catalyzes the elongation stage of translation. A functionally impaired eEF2, due to a heterozygous missense variant in the EEF2 gene, was previously reported in one family with spinocerebellar ataxia-26 (SCA26), an autosomal dominant adult-onset pure cerebellar ataxia. Clinical exome sequencing identified de novo EEF2 variants in three unrelated children presenting with a neurodevelopmental disorder. Individuals shared a mild phenotype comprising motor delay and relative macrocephaly associated with ventriculomegaly. Populational data and bioinformatic analysis underscored the pathogenicity of all de novo missense variants. eEF2 yeast model strains demonstrated that patient-derived variants affect cellular growth, sensitivity to translation inhibitors and translational fidelity. Consequently, we propose that pathogenic variants in the EEF2 gene, so far exclusively associated with late-onset SCA26, can cause a broader spectrum of neurologic disorders, including childhood-onset neurodevelopmental disorders and benign external hydrocephalus.

Late-Onset Anaphylaxis to Omalizumab Reported

2006 ◽  
Vol 37 (6) ◽  
pp. 6
Author(s):  
PATRICE WENDLING
Keyword(s):  
Late Onset
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